Longitudinal study of infants with high grade vesicoureteral refluxhigh-grade vesicoureteral reflux

S fi Sjö t öSofia Sjöström

Department of PediatricsInstitute of Clinical Sciencesat Sahlgrenska Academy

UNIVERSITY OF GOTHENBURG

i f bli iList of PublicationsI. Sjostrom S., Sillén U., Bachelard M., Hansson S. and Stokland E.,

Spontaneous resolution of high grade infantile vesicoureteral reflux.J Urol, 2004. 172(2): p. 694-8; discussion 699.

II. Sjostrom S., Jodal U., Sixt R., Bachelard M. and Sillén U.,Longitudinal Development of Renal Damage and Renal Function i I f t With Hi h G d V i t l R flin Infants With High Grade Vesicoureteral Reflux.J Urol, 2009. 181, 2277-2283.

III Sjostrom S Bachelard M Sixt R and Sillén UIII. Sjostrom S., Bachelard M., Sixt R. and Sillén U., Change of urodynamic patterns in infants with dilating vesicoureteral reflux;three year followup.J Urol 2009 182(5):2453-4J Urol, 2009. 182(5):2453-4 .

IV. Sjostrom S., Jodal U., Stokland E., Sixt R., Wahll L., and Sillén U.,Predictive factors for resolution of high-grade infantile vesicoureteralPredictive factors for resolution of high grade infantile vesicoureteral reflux.-Results of uni and multivariate analyses.J Urol, 2010. 183(3), 1177-1184.

h iResearch questions•What is the spontaneous resolution rate in dilated infantile VUR and which factors affect the outcome? C l t ti t ith hi h h f l ti f th Can we select patients with a high chance of resolution from those with a low probability of resolution?

•What is the frequency of renal abnormality in dilated infantile VUR and how many have impaired renal function? y pCan we identify riskfactors for deterioration of renal status?

Wh t th bl dd f ti h t i ti i i f til dil t d •What are the bladder function characteristics in infantile dilated VUR and do they change during the first years of life? How many develop bladder dysfunction?develop bladder dysfunction?

S d d iStudy design

Prospective longitudinal observational study.p g yEligable; Children with primary dilated vesicoureteral reflux (grade III V) diagnosed vesicoureteral reflux (grade III-V) diagnosed during the first year of life.Monitoring of renal status, bladder function and natural course of reflux over time.

i lMaterial

Paper I, II, IV III

Patients, year of birth 1992-1997 1992-97 / 1998-99

Number of patients 115 114 ( 94 / 20 )p ( )

Sex, N (%) : boys girls

80 (70%)35 (30%)

89 (78%)25 (22%)girls 35 (30%) 25 (22%)

Presentation: prenatal 30 (26%) 30 (26%)UTIother

82 (71%)3 (3%)

84 (74%)

G d f i l iGrade of VUR at inclusion

40

s

30

35

patie

nts

15

20

25

GirlsBoysm

ber o

f p

5

10

15 Boys

Num

0

5

Grade III Grade IV Grade V

h dMethodsNumber of investigations per child

Age at first investigationMedian months

Follow-up time

Median monthsper child Median (range)

Median months (range)

Median months (range)

VCM, (VCU) & 3 (2-5) 2.7 (0.03-12) 36 (2-69)( )Free voiding studies

( ) ( ) ( )

Scintigrams 4 (1 10) 4 7 (0 2 54) 62 (4 135)Scintigrams (DMSA&MAG3)

4 (1-10) 4.7 (0.2-54) 62 (4-135)

Clearance 3 (1-11) 7.7 (0.5-72) 53 (1-145)(51Cr-EDTA-clearance)

lResultsComplete resolution of VUR in 30 (26%)Downgrading of VUR to grade I-II in 14 (12%) Probability of dilated VURA. Split by grade of VUR at inclusion

Log-Rank test:p=0.003

All patients

ng re

flux

0.7

0.8

0.9

1.0

Log-Rank test:

All patients

0.9

1.0

All ti t

B. With or without breakthrough infections

C With or without bladder dysfunction

Not cured

Grade at entry345

Pro

babi

lity

of d

ilatin

0.2

0.3

0.4

0.5

0.6Log-Rank test:

p=<.001

Breakthrough infectionity o

f dila

ting

reflu

x

0.4

0.5

0.6

0.7

0.8

Log-Rank test:p=<.001

All patients

ng re

flux

0.7

0.8

0.9

1.0

C. With or without bladder dysfunction

n=18 7 3n= 52 39 25 16 8 5 4n= 45 34 29 18 12 5 5

0.0

0.1

Years of follow-up after first VCU0 1 2 3 4 5 6 7 Not cured

n= 61 37 23 11 8 Non= 54 43 34 25 13 5 Yes

gNo

Yes

Prob

abil

0.0

0.1

0.2

0.3

0 1 2 3 4 5 6 7N t d

Bladder dysfunctionNo

Yes

Prob

abilit

y of

dila

tin

0.2

0.3

0.4

0.5

0.6

Years of follow-up after first VCUNot curedn= 44 21 11 6 Non= 42 38 30 21 12 5 Yes

0.0

0.1

Years of follow-up after first VCU0 1 2 3 4 5 6 7

lResults

Independent variables negatively associated to VUR resolution in multivariate analyses

Variable Hazard Ratio (95% CI) p-valueRenal abnormality 0 43 (0 29-0 63) <0 0001Renal abnormality 0.43 (0.29 0.63) <0.0001

Bladder dysfunction 0.36 (0.24-0.53) <0.0001

Breakthrough UTI 0.49 (0.25-0.97) 0.0397

C l iConclusion

The spontaneous resolution rate in infantile high-grade VUR:infantile high-grade VUR:-Is high (Resolution or downgrading in 38%)I hi h i b d i th i f t -Is higher in boys during the infant year

-Is negatively associated with breakthrough infections, bladder dysfunction, higher grades of VUR and y , g grenal abnormalities.

C l iConclusion

Multivariate analysesMultivariate analyses

Renal damage Bladder dysfunctionRenal damage, Bladder dysfunctionand Breakthrough UTIhave shown to be three strong independent factors for prediction of resolution of VUR pin multivariate analyses.

lResults

0.9

1.0

0.9

1.0

0.9

1.0

atus

Probability of unchanged or deteriorated renal statusf u

ncha

nged

rena

l sta

tus

0 4

0.5

0.6

0.7

0.8

Breakth0 4

0.5

0.6

0.7

0.8

Uni or bilater0 4

0.5

0.6

0.7

0.8

Rena

Breakthrough UTI No/Yes

unch

ange

d ren

al st

Uni or bilateral renal abnormality

Renal function (GFR)Normal/Subnormal

Prob

abilit

y of

0.0

0.1

0.2

0.3

0.4

0 1 2 3 4 5 6 7 8

Unchanged status

Log-Rank test:p=0.041

n= 56 55 49 44 33 26 21 15 1n= 52 51 44 41 31 22 15 6 5

0.0

0.1

0.2

0.3

0.4

Unchanged status

Log-Rank test:p=0.038

n= 27 26 23 18 16 11 8 5n= 71 70 63 61 46 36 28 16

0.0

0.1

0.2

0.3

0.4

0 1 2 3 4 5 6 7 8

Unchanged status

Log-Rank test:p=0.001

n= 32 31 25 22 19 13 10 5n= 75 74 67 63 45 35 26 17 1

Prob

abilit

y of u

Breakthrough UTI, bilateral renal damage and subnormal GFR were predictors for deterioration in renal status

Years of follow-up0 1 2 3 4 5 6 7 8

Years of follow-up0 1 2 3 4 5 6 7 8

Years of follow-up0 1 2 3 4 5 6 7 8

Years of follow-up Years of follow-up Years of follow-up

were predictors for deterioration in renal status.Deterioration was more frequent in prenatally diagnosed patients (p=0.047) (p 0.047)

C l iConclusionThe frequency of renal abnormalityin infantile dilated VUR is high (85%).g ( )Subnormal renal function is seen in 30%.

Renal status-Remains unchanged in the majority (82%) during the first years of life.-Breakthrough UTI, bilateral renal damage and subnormal renal function are predictors for deterioration in renal status.

ResultsResultsTYPE OF BLADDER DYSFUNCTION

•HIGH CAPACITY &

Bladder dysfunction was found in 48 (42%) of study patients

•HIGH CAPACITY & INCOMPLETE EMPTYING34 of 48 (71%)34 of 48 (71%)•OVERACTIVE CONTRACTIONS14 of 48 (29%)14 of 48 (29%)

C l iConclusion

In infants with ditated VUR:Bladder dysfunction is common-Bladder dysfunction is common.

-The urodynamic pattern changes during the first f lifyears of life.

-High pressure and low capacity turns into high capacity with incomplete emptying.-Bladder dysfunction can only be diagnosed from adde dys u ct o ca o y be d ag osed othe second year of life and is seen in almost half of the patientsof the patients.

G l C l iGeneral Conclusion

This observational study has resulted in: d t il d d i ti f th h t i ti d -a detailed description of the characteristics and

course of dilated VUR in infants. d i ti f h i d i d i th -a description of changes in urodynamics during the

first years of life. d i ti f l t t t i l i d -a description of renal status at inclusion and over

time.i k f t ff ti th t h b -risk factors affecting the outcome have been

identified.

Cli i l li iClinical Implications

Our study has provided tools for distinguishing infants with a high chance of spontaneous infants with a high chance of spontaneous resolution from those with a high risk of remaining dilated refluxdilated reflux.

The study results can be used to formulate hypotheses for future management of infants with dilated VUR.

Thank You!

The doctoral thesis Longitudinal study of infants Longitudinal study of infants with high-grade vesicoureteral refluxis avaliable on internet

http:hdl handle net/2077/20459http:hdl.handle.net/2077/20459